Responsible Use of Oral Corticosteroids in People with Comorbid Diabetes: An Expert Consensus.

Globally, diabetes mellitus (DM) is a substantial contributor to morbidity and mortality. Comorbidities and intercurrent illnesses in people with diabetes may necessitate the use of steroids. Acute as well as chronic use of steroids contributes substantially to the development of various complications. Despite this, there are no standard guidelines or consensus to provide a unified approach for the rational use of steroids in people with diabetes. Also, there is scant harmonization among clinicians with the use of different steroids in routine practice. To address the inconsistencies in this clinical arena, the consensus working group (CWG) formulated a unified consensus for steroid use in people with diabetes. In people with diabetes, the use of steroids causes hyperglycemia and may precipitate diabetic ketoacidosis (DKA). An increase in weight is directly related to the dose and duration of the steroid therapy. Steroid-related alterations in hyperglycemia, dyslipidemia, and hypertension (HTN) add to the increased risk of cardiovascular (CV) disease. The risk of complications such as infections, osteoporosis, myopathy, acne, cataracts, and glaucoma may increase with the use of steroids. Appropriate and timely monitoring of these complications is necessary for early detection and treatment of such complications. Given the systemic effects of various antihyperglycemic drugs, there is a possibility of aggravating or diminishing the specific complications. Preference to a safer steroid is required matching the steroid dose equivalence and individualizing patient management. In conclusion, short-, intermediate-, or long-term use of steroids in people with diabetes demands their rational use and holistic approach to identify, monitor, and treat the complications induced or aggravated by the steroids.

Comparison of the efficacy, safety, and tolerability of the FDC of telmisartan + bisoprolol with telmisartan + metoprolol succinate ER combination therapy for stage 1 and stage 2 hypertension: A double-blind, multicentric, phase-III clinical study.

AIM: The present study compared the safety, efficacy, and tolerability of the new fixed-dose combination (FDC) of telmisartan 40 mg + bisoprolol 5 mg (TBP) tablets with the existing comparator FDC telmisartan 40 mg + metoprolol succinate ER 50 mg (TMS) tablets in patients with stage 1 and stage 2 hypertension. METHODOLOGY: The multicentric, double-blind, parallel-group, comparative, prospective, phase-III clinical study involved 264 subjects with stage 1 and stage 2 hypertension from 10 centres across India. The selected subjects were randomized into two groups: group A received the TMS and group B received the new FDC TBP. The primary endpoint was the mean change in seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) from baseline to week 12 in both the control and study arms. The secondary endpoint was achieving the target of SeSBP <140 mmHg and SeDBP <90 mmHg from baseline to week 12 in both groups. Safety and tolerability parameters were evaluated in both groups based on adverse effects (AEs) reported by the patients and the physician. RESULTS: Both treatment groups exhibited a reduction in BP after 2 weeks of treatment, which was sustained until 12 weeks. The mean change in SeSBP and SeDBP at weeks 2, 6, and 12 compared to the previous visit showed statistical significance (p < 0.001) in all cases for both groups A and B. The mean changes in SeSBP and SeDBP from baseline to study end were numerically higher in group B than in group A. The mean difference in SeSBP from baseline to study end was significantly higher in group B compared to group A (p = 0.029). By week 12, 88.28 % and 89.84 % of subjects in group B achieved SeSBP <140 mmHg and SeDBP <90 mmHg respectively, while 86.71 % and 91.40 % of subjects in group A achieved the same targets. Reported AEs were mostly mild to moderate in both treatment groups, and no serious AEs or deaths were reported. Tolerability was rated as 'excellent' by 93.75 % of subjects in group B and 91.40 % of subjects in group A. CONCLUSION: Both the new FDC TBP and the existing comparator TMS combination therapy have comparable efficacy, tolerability, and safety for the management of stage 1 and stage 2 hypertension. TRIAL REGISTRY NAME: Clinical Trials Registry of India (CTRI) TRIAL REGISTRATION NO: CTRI/2021/11/037,926 PROTOCOL NO: MLBTL/05/2021 PROTOCOL URL: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=62069&EncHid=&userName=bisoprolol.

Association of Physicians of India Expert Recommendations on Oral Fluid, Electrolytes, and Energy Management during Transition Care and Discharge for Hospitalized Patients with Nondiarrheal Illnesses.

Acute nondiarrheal illnesses (NDIs) involve overt or subclinical dehydration, requiring rehydration and electrolyte repletion. Dehydration is frequently under-recognized and under-managed, both in outpatient departments (OPDs) and inpatient departments (IPDs). Postadmission dehydration is associated with longer hospital stays and higher inhospital mortality rates. Recognizing and understanding dehydration in hospitalized patients is necessary due to the adverse outcomes associated with this condition. In this article, we aimed to develop practical consensus recommendations on the role of oral fluid, electrolyte, and energy (FEE) management in hospitalized patients with FEE deficits in NDI. The modified Delphi consensus methodology was utilized to reach a consensus. A scientific committee comprising eight experts from India formed the panel. Relevant clinical questions within three major domains were formulated for presentation and discussion: (1) burden and factors contributing to dehydration in hospitalized patients; (2) assessment of fluid and electrolyte losses and increased energy requirements in hospitalized patients; and (3) management of FEE deficits in hospitalized patients [at admission, during intravenous (IV) therapy, IV to oral de-escalation, and discharge]. The consensus level was classified into agreement (mean score ≥4), no consensus (mean score <4), and exclusion (mean score <4 after the third round of discussion). The questions that lacked agreement were discussed during the virtual meeting. The experts agreed that the most common factors contributing to dehydration in patients with NDI hospitalized in IPDs include decreased oral fluid intake, increased fluid loss due to the illness, insensible fluid loss, and a lack of awareness among doctors about dehydration, which can result in poor fluid intake. Time constraints, discontinuity of care, lack of awareness of the principles of fluid balance, lack of formal procedures for enforcing hydration schemes, and lack of adequate training are most often barriers to the assessment of hydration status in hospital settings. Experts used hydration biomarkers, such as changes in body weight, serum, or plasma osmolality; fluid intake; and fluid balance charts; along with urine output, frequency, quantity, and color, to determine hydration status in hospital settings. Experts agreed that appropriate FEE supplementation in the form of ready-to-drink (RTD) fluids can restore FEE deficits and shorten the length of hospital stays in hospitalized patients at admission, during de-escalation from IV to oral therapy, and at discharge. RTD electrolyte solutions with known concentrations of electrolytes and energy are good choices to avoid taste fatigue and replenish FEE in hospitalized patients during transition care and at discharge.

Pre-Basal Insulin Analog Era: Paving the Way for Modern Day Basal Insulins.

Prior to the discovery of insulins, diabetes was managed predominantly by dietary interventions. Discovery of insulin and its first human trial highlighted the need for higher purity insulin thereby steering the subsequent journey of insulin development. Considering the limitations of the early preparations like short duration of action and need for several injections per day, attempts at protracting the duration of insulin action were made. This led to the development of intermediate-acting Neutral Protamine Hagedorn (NPH) and the Lente family of insulins. This review provides insights into the discovery of insulins and the shortcomings of early protracted release preparations, which in turn, gave impetus to the search for a 'true' basal insulin, which could mimic the endogenous human basal insulin secretion.

Immunogenicity, Safety, and Tolerability of Live Attenuated VaricellaZoster Virus Vaccine (ZOSTAVAX™) in Healthy Adults in India.

BACKGROUND: Herpes zoster (HZ) is caused by varicella-zoster virus ( VZV ) reactivation. In the United States, Zoster vaccine (ZOSTAVAX) is indicated for HZ prevention in patients ≥50 years. AIMS: To evaluate the immunogenicity, safety, and tolerability of ZOSTAVAX in healthy Indian subjects, to support its registration in India. METHODS: This open-label, single-arm study was conducted at 10 sites in India. Healthy Indians (≥50 years) received a single ZOSTAVAX dose. Immunogenicity was assessed by VZV-specific antibody titer using gpELISA assay. VZV-specific antibody geometric mean titers (GMT; Day 1 pre-vaccination, Week 6 post-vaccination) and geometric mean fold-rise (GMFR; Week 6 post-vaccination) were assessed. Safety was evaluated by the incidence of adverse events (AEs) and serious adverse events (SAEs) within 42 days of vaccination. Two-sided 95% confidence intervals (CIs) were evaluated using t-distribution with natural log-transformed values. RESULTS: Of the 250 subjects (mean age, 58.6 years) enrolled and vaccinated, 244 subjects completed the 6-week follow-up. Overall, subjects in the per-protocol population had GMT of 149.8 gpELISA units/mL (n=250; 95% CI: 132.6, 169.2) at Day 1 pre-vaccination, and 410.8 gpELISA units/mL (n=243; 95% CI: 373.0, 452.6) at Week 6 post-vaccination. GMFR of VZV-specific antibody from Day 1 pre-vaccination to Week 6 post-vaccination was 2.8 (95% CI: 2.5, 3.1). Overall, 67 subjects (26.8%) experienced AEs, with 48 (19.2%) reporting injection-site AEs and 38 (15.2%) reporting non-injection-site AEs. SAE-abdominal pain and bronchitis-was reported in one (0.4%) patient each. There was one death, which was unrelated to the vaccine. LIMITATIONS: Since ZOSTAVAX introduces a new live attenuated virus, clinical reactivation of ZOSTAVAX virus and wild-type VZV will need to be differentiated. CONCLUSIONS: In healthy Indians ≥50 years, ZOSTAVAX was well tolerated and resulted in expected VZV-specific antibody titer levels at 6 weeks post-vaccination.